Breastfeeding accounts for nearly half of mother-to-child transmission of HIV-1 (MTCT). Safe and affordable alternatives to breastfeeding are not available for the majority of infants born to HIV-1 infected women. Numerous studies support the role of mastitis in increasing breastfeeding transmission, likely from the increase in breast milk HIV-1 load associated with mastitis. Clinical mastitis characterized by pain, redness and swelling, occurs in up to one-third of lactating women. Subclinical mastitis, without symptoms, but with increased breast milk sodium ([Na+]), is even more prevalent and has also been associated with increases breast milk RNA viral load and MTCT. These findings suggest that the prevention or treatment of mastitis has the potential to greatly reduce MTCT. Such strategies require knowledge of the etiologies of mastitis. There are no published studies elucidating the etiologies of subclinical mastitis, nor mastitis in HIV-1 infected women. Veterinary studies of mastitis implicate a broad range of bacteria, mycobacteria, fungi, mycoplasmas and herpes group viruses. We hypothesize that mastitis, especially subclinical mastitis, in HIV- 1 infected women is also caused by a variety of organisms. In addition, that mastitis increases milk HIV-1 load within the breast, independent of the blood, presumably by immune stimulation of latently infected cells (this would occur even during HAART, unless protease inhibitors are given). In this proposal we aim to: [unreadable] [unreadable] 1. Determine the association of mastitis, as defined by elevated breast milk [Na+], to breast milk and blood HIV-1 RNA and DNA, and to breast milk inflammatory cells in HIV-1 infected women in Zimbabwe. [unreadable] [unreadable] 2. Determine the infectious etiologies of mastitis in these HIV-1 infected women; the utility of breast milk [Na+] in prediciting specific pathogens; and the milk HIV-1 loads associated with specific pathogens. By identifying the infectious agents associated with high levels of HIV-1 in breast milk, treatment and prophylaxis strategies can be developed that may reduce HIV-1 transmission to breastfeeding infants. [unreadable] [unreadable] [unreadable]